Massachusetts Alzheimer?s Disease Research Center: Clinical Core The Clinical Core of the Massachusetts Alzheimer?s Disease Research Center (MADRC) parallels that of the MADRC as a whole: to support research into the causes, mechanisms and treatment of Alzheimer?s disease and Alzheimer-related disorders (AD/ADRD), with the eventual goal of cure and even prevention. To facilitate research in these areas, we are revamping our Research Cohort of men and women from diverse ethnic and racial backgrounds to achieve a larger number and greater diversity of impaired participants and pursue universal deep clinical, imaging, and molecular phenotyping. This will enable the Cohort to serve as our Center?s ?laboratory? to understand disease heterogeneity and accelerate treatments for AD/ADRD. To accomplish these goals, we have three sets of Aims: The first group (Aims 1-4), intended to marshal resources, focuses on developing and maintaining a well- characterized Research Cohort to ensure that we have sufficient numbers of MCI and dementia across AD/ADRD. We bolster our recruiting of impaired individuals across AD/ADRD, and will submit annual UDS evaluations to NACC and sample our participants for genetic, fluid, and imaging biomarkers, plus obtain consent for brain donation. We also maintain a database of patients from the affiliated MGH Memory Division clinics (Memory Disorders, FTD and DLB) to refer a larger pool of ?research ready? participants (Research Cohort plus Clinic Patients) to a wide range of local and national observational studies and clinical trials. The second group (Aims 5-6), intended to develop new strategies, focuses on achieving universal deep phenotyping of our Research Cohort and developing and validating novel clinical instruments for early detection for use in clinical settings and clinical trials. We will use our Research Cohort, with deep clinical, imaging and molecular phenotyping, as our Center?s ?laboratory? to test hypotheses about clinical and biological differences and commonalities in AD/ADRD and to develop and validate biomarkers that may expedite target discovery and clinical trial process. We will continue to share our data and discoveries with other ADRCs and the broader scientific community for validation and implementation. The final group (Aims 7-8), intended to build the future, focuses on training future generations clinician- scientists and on promoting dementia prevention efforts and research opportunities to individuals in the community, particularly those from underserved minorities. These efforts will be done in close collaboration with REC and ORE Core. We aim to engage all stakeholders - patients, caregivers, clinicians and researchers - as direct partners to accelerate toward a cure for AD/ADRD.